Desmoglein 1 deficiency results in severe dermatitis, multiple allergies and metabolic wasting

Nat Genet. 2013 Oct;45(10):1244-1248. doi: 10.1038/ng.2739. Epub 2013 Aug 25.


The relative contribution of immunological dysregulation and impaired epithelial barrier function to allergic diseases is still a matter of debate. Here we describe a new syndrome featuring severe dermatitis, multiple allergies and metabolic wasting (SAM syndrome) caused by homozygous mutations in DSG1. DSG1 encodes desmoglein 1, a major constituent of desmosomes, which connect the cell surface to the keratin cytoskeleton and have a crucial role in maintaining epidermal integrity and barrier function. Mutations causing SAM syndrome resulted in lack of membrane expression of DSG1, leading to loss of cell-cell adhesion. In addition, DSG1 deficiency was associated with increased expression of a number of genes encoding allergy-related cytokines. Our deciphering of the pathogenesis of SAM syndrome substantiates the notion that allergy may result from a primary structural epidermal defect.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Child, Preschool
  • Dermatitis / genetics*
  • Desmoglein 1 / genetics*
  • Female
  • Humans
  • Hypersensitivity / genetics*
  • Infant
  • Male
  • Mutation
  • Severity of Illness Index
  • Syndrome
  • Wasting Syndrome / genetics*
  • Wasting Syndrome / metabolism


  • Desmoglein 1

Associated data

  • RefSeq/NM_001942